PCSK9 and endothelial dysfunction: Potential explanations for this discordance between patient genotype and serum protein concentrations with endothelial dysfunction markers include 1) although 90% of circulating PCSK9 is secreted by the liver, another major source of PCSK9 is vascular smooth muscle cells.24 Thus, it is conceivable that PCSK9 LOF genotype results in lower local levels of PCSK9 essential to endothelial health, which are unmeasurable when sampling patient serum.